a placebo-controlled study of safety and effectiveness of myozyme (alglucosidase alfa) in patients with late-onset pompe disease

Conditions: Pompe Disease (Late-onset); Glycogen Storage Disease Type II (GSD-II); Acid Maltase Deficiency Disease; Glycogenosis 2

Summary: pompe disease (also known as glycogen storage disease type ii) is caused by a deficiency of a critical enzyme in the body called acid alpha-glucosidase (gaa). normally, gaa is used by the body's cells to break down glycogen (a stored form of sugar) within specialized structures called lysosomes. in patients with pompe disease, an excessive amount of glycogen accumulates and is stored in various tissues, especially heart and skeletal muscle, which prevents their normal function. the overall objective is to evaluate the safety, efficacy, and pharmacokinetics (pk) of alglucosidase alfa treatment in patients with late-onset pompe disease as compared to placebo.


Eligibility criteria:
inclusion criteria: * patient must provide signed, informed consent prior to performing any study-related procedures. * patient must have a diagnosis of pompe disease based on deficient endogenous gaa activity in cultured skin fibroblasts of less than or equal to 40% of the normal mean of the testing laboratory and 2 confirmed gaa gene mutations; * patient must be greater than or equal to 8 years of age at the time of enrollment; * patient must be able to ambulate 40 meters (approximately 130 feet) in 6 minutes on each test performed on two consecutive days (use of assistive devices such as a walker, cane, or crutches, is permitted); * patient must have an fvc of greater than or equal to 30% and \< 80% predicted in the upright position; * patient must have a postural drop in fvc (liters) of at least 10% from the upright to the supine position; * patient must have proximal muscle weakness in the lower limbs based on unilateral qmt of the knee extensors defined as \< 80% of the predicted value based on age, gender and body size * patient must be able to tolerate pulmonary function testing (pft) and muscle testing in the supine position; * patient must have testable muscle in bilateral knee flexors and knee extensors, and testable muscle in bilateral elbow flexors and elbow extensors; * patient must be able to provide reproducible muscle and pulmonary function test results; * patient (and patient's legal guardian if patient is \< 18 years of age) must have the ability to comply with the clinical protocol; * a female patient of childbearing potential must have a negative pregnancy test (urine) at baseline. note: all female patients of childbearing potential and sexually mature males must use a medically accepted method of contraception throughout the study. exclusion criteria: * patient requires the use of invasive ventilatory support; * patient requires the use of noninvasive ventilatory support while awake and in an upright position; * patient has received enzyme replacement therapy with gaa from any source; * patient has used an investigational product within 30 days prior to study enrollment, or is currently enrolled in another study which involves clinical evaluations, unless prior approval is given by genzyme; * patient has a major congenital anomaly, medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities;

Keywords: glycogen storage disease type ii gsd-ii pompe disease